Mycetomas are chronic, granulomatous, subcutaneous infections caused by either eumycetes fungi or actinomycetes bacteria, giving rise to eumycetomas and actinomycetomas, respectively. The disease is endemic in many tropical countries, and is characterized by slow progression with risks of bone and visceral involvement. Treatment consists of long courses of antifungals and antibacterials, often combined with surgery. Drug resistance, poor response to treatment, and high rates of relapse have prompted trials of novel antibiotics and antifungals. This article discusses the potential of new treatment regimens and recent developments and improvements in diagnostics and prognostics, which will improve disease management.